The present invention relates to the field of ophthalmic solutions and especially to the aspects of preservative efficacy and comfort after prolonged use. These ophthalmic solutions have been used for some period of time and are available as over the counter products. Solutions that are used in direct contact with corneal tissue such as the delivery of active pharmaceutical agent to the eye, or indirectly, such as the cleaning, conditioning or storage of devices that will come in contact with corneal tissue, such as contact lenses, there is a need to insure that these solutions do not introduce sources of bacterial or other microbial infection. Thus preservatives are included to reduce the viability of microbes in the solution and to lessen the chance of contamination of the solution by the user since many of the solutions are bought, opened, used, sealed and then reused.
State of the art preservative agents include polyhexamethylene biguanide (phmb), polyquad (trademark), chlorhexidine, and benzalkonium chloride, and the like, all of which at some concentration irritate corneal tissue and lead to user discomfort. Therefore, a solution that employs a given amount of a preservative agent, but which is made more effective by addition of an agent that is not a preservative agent would be desired.
The present invention relates to improved ophthalmic solutions that employ allantoin in order to more effectively preserve solutions and to reduce the degree to which cationic preservatives will deposit on contact lenses. Ophthalmic solutions are here understood to include contact lens treatment solutions, such as cleaners, soaking solutions, conditioning solutions and lens storage solutions, as well as wetting solutions and in-eye solutions for treatment of eye conditions.
The solutions specifically described herein have 0.001 to about 1 percent of allantoin in combination with other active ingredients useful in ophthalmic solutions such as tonicity agent, buffers, preservatives, surfactants, and antimicrobial agents. The preservatives that are specifically useful are catirnic preservatives such as polyhexamethylene biguanide (phmb), polyquad (trademark), chlorhexidine, and benzalkonium chloride, as well as other cationic preseratives that may prove useful in the present invention as well. The cationic preservatives are used at effective amounts as preservatives, and in the instance of PHMB from 0.0001 percent by weight to higher levels of about 0.01 weight percent. It was found that an unexpected preservative efficacy was displayed when allantoin was used in conjunction with the cationic preservative. These cationic preservatives can be used in the range of 1 to 100 parts per million, or in amounts of at least one part per million. The other components of the solution are used at levels known to those skilled in the art in order to improve the wearability of lenses and when used directly in the eye, to provide increased resistance to infection. Allantoin used in ophthalmic solution increases preservative efficacy in certain formulations, provides increased resistance to infection in corneal tissue, in certain formulations, and improves the quality of tears in certain formulations.
The formulations may also include buffers such as phosphates, bicarbonate, citrate, borate, ACES, BES, BICINE, BIS-Tris, BIS-Tris Propane, HEPES, HEPPS, irnidazole, MES, MOPS, PIPES, TAPS, TES, and Tricine
Surfactants that might be employed include polysorbate surfactants, polyoxyethylene surfactants, phosphonates, saponins and polyethoxylated castor oils, but preferably the polyethoxylated castor oils. These surfactants are commercially available. The polyethoxylated castor oils are sold by BASF under the trademark Cremaphor(copyright).
Specific embodiments might include contact lens solution further comprising a osmotic agent selected from the group consisting of trehalose, mannitol, sorbitol, lactulose, sodium chloride, and propylene glycol. Alternately embodiments might include a solution with between 0.01% and 5.0% glycerin. Still further the invention can include between 0.01% and 2.0% of decanedioic acid and further comprise a sequestering agent selected from the group consisting of ethyltenediaminetetraacetic acid, phosphonates, citrate, gluconate and tartarate.
Allantoin and the other agents used in the present invention are all commercially available, and well enough understood to be formulated into products within the scope of the invention by those skilled in the art.